Thebaine is an N-methylmorphinan having the structure: 
Thebaine or an acid salt thereof is an intermediate that is useful for making a variety of morphine alkaloids, in particular 14-hydroxymorphinans, such as oxycodone. Morphine alkaloids are useful for treating pain.
The following references describe processes for making thebaine:
U.S. Pat. No. 3,894,026 to Sohar et al. describes a method for preparing thebaine from salutarindol.
U.S. Pat. No. 4,045,440 to Rapaport et al. and R. Barber et al., J. Med. Chem. 18(11):1074–1077 (1975) describe a method for making thebaine by reacting codeine with potassium hydride and methyl iodide to provide the O-6 methyl ester of codeine, and then oxidizing the 0–6 methyl ester of codeine with MnO2 in tetrahydrofuran.
U.S. Pat. No. 6,090,943 to Mudryk et al. describes a method for making thebaine by reacting codeinone with a metal alkoxide, such as potassium tert-butoxide, in a solvent that does not react with the codeinone or metal alkoxide, such as N-methylpyrrolidone, then reacting the resultant product with a methylating agent, such as dimethylsulfate.
D. H. R. Barton et al., J. Chem. Soc. 2423–2438 (1965) describes a synthesis of salutaridine and a method for converting it to thebaine.
H. Rapoport et al., J. Amer. Chem. Soc. 89(8):1942–1947 (1967) describes a method for making thebaine by reacting codeinone dimethyl ketal with phosphorous oxychloride in pyridine.
T. Kametani et al., J. Chem. Soc. (C) 2030–2033 (1969) describes a method for making thebaine by diazotizing (±)-1-(2-amino-3-benzyloxy-4-methoxybenzyl)-1,2,3,4-tetrahydro-6,7-dimethoxy-2-methylisoquinoline, thermally decomposing the resultant diazonium salt to provide (±)-salutaridine, and converting the (±)-salutaridine to thebaine.
M. Schwartz et al., J. Amer. Chem. Soc. 97(5):1239–1240 (1975) describes a method for making thebaine from N-trifluoroacetylnorreticuline and N-ethoxycarbonylnorreticuline.
A. Coop et al., Heterocycles 49:43–47 (1998) describes a method for making thebaine by reacting codeinone with potassium tert-butoxide in the presence of 18-Crown-6 and adding dimethyl sulfate.
Despite these described methods, there remains a need for improved methods for making thebaine and its acid salts.
Citation of any reference in Section 2 of this application is not an admission that the reference is prior art to the application.